CPV is primarily an enteric pathogen of CANIDAE. It causes an infection in dogs, especially young dogs, which frequently leads to an enteric disease characterised by acute diarrhoea, fever and leukopenia. It can cause high mortality/high morbidity in infected animals. CPV is genetically and antigenically closely related to Feline panleukopenia virus (FPV), Mink enteritis virus (PEV), Raccoon parvovirus (RPV) and is considered to be a host range variant of one of these viruses.
Vaccines have been developed to prevent parvoviral infection of target animals such as dogs, cats, mink, raccoon, and cattle, in particular dogs and cats. CPV and FPV can be effectively controlled by vaccination with live attenuated CPV and FPV, respectively. Puppies can be protected when maternally derived antibodies are present, by specially developed live attenuated vaccines only, such as described for example in WO 9102054. Such vaccines suffer from the disadvantage that modified live vaccine virus could be excreted post vaccination. The use of an inactivated, adjuvanted preparation, however, may be regarded as safer as no live virus can be excreted post vaccination. Higher concentrations of inactivated vaccine are required to stimulate an antibody response, particularly in the presence of maternally derived antibody (MDA). However, the presence of high titres of MDA can prevent effective vaccination with inactivated vaccines.
In some puppies the passive immunity to certain antigens can persist for a considerable period (4 months or more) at levels sufficient to interfere with vaccination. As the MDA level declines a puppy may be protected insufficiently against infection and disease, but still be refractory to vaccination. Hence, these puppies remain unprotected during a considerable period in their early life. The danger of infection of complete litters poses a serious risk, particularly after the maternally derived immunity has vanished. The potential risk of infection due to the presence of MDA was known for dogs, but has recently been recognized to affect certain neonates of other animals as well, in particular in MDA positive offspring of cats, minks and raccoons.
Recent developments in the vaccine field have resulted in a novel class of vaccines based on the induction of immunity following the delivery of plasmid DNA encoding immunogenic proteins. Such vaccines may hold the promise of protecting against disease by inducing both humoral and cell-mediated immune response, without many of the disadvantages associated with vaccines presently in use.
Whilst it was hoped that the efficacy of DNA immunization would not be reduced by maternally derived antibodies, in practice it has been found that vaccination of one-day-old piglets against pseudorabies, using plasmid DNA incorporating the gD glycoprotein gene of pseudorabies, did not result in significant protection. Piglets from immune sows neither developed an antibody response, nor were primed against pseudorabies virus, as demonstrated by the antibodies kinetics after challenge (see Monteil, M. et al., Vet. Res. (1996), 27, 443-452).
In a recent abstract it has been briefly reported that "immunization of dogs with a range of doses of a plasmid encoding the major capsid proteins of canine parvovirus (VP-1, VP-2) resulted in the dose dependent appearance of anti-parvovirus antibodies at significant levels". From the subsequent challenge of the dogs, with a mixture of virulent parvovirus strains, it was evident that all immunized dogs were protected against infection and disease. No mention was made in the abstract of the nature of the construct used. Furthermore, there was no reference to the age of the dogs and their immune status.
One of the main limitations of vaccination concerns the vaccination of the young offspring of immune females. In all species the existence of maternal antibodies is a strong limitation which impairs the development of an immune response in the young.